P1281: REFRACTORY PATIENTS WITH FAVORABLE/INTERMEDIATE-RISK AML BENEFIT FROM AZACYTIDINE MAINTENANCE THERAPY AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Xinhui Zheng, Yigeng Cao, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Recurrence after allo‐HSCT is the primary cause of treatment failure for patients with myeloid malignancy. AZA maintenance has been considered a promising therapy to prevent relapse and improve survival, nevertheless, the efficacy still remains controversial. Aims: The trial was conducted to explore whether moderate-dose AZA maintenance following allo-SCT had a positive impact on survival for patients with a high risk of recurrence. Methods: We conducted the prospective clinical trial and patients 15 to 65 years of age who had AML, MDS, or CMML and underwent allo-HSCT were screened. Patients with AML were eligible if they had adverse risk according to ELN 2017, relapsed/refractory disease, detected MRD before transplantation, or MDS or CMML transformation to AML. Patients with MDS were eligible if they had the diagnosis of MDS-EB2, poor karyotype, very high-risk disease by the IPSS-R, or TP53 mutation. In the trial, 78 patients were enrolled in the AZA group between September 2019 and April 2022. AZA was applied 50 mg/m2 subcutaneously or intravenously daily for 5 days from day +60 post-SCT in a 28-day period. The control group was comprised of 108 patients who met the inclusion criteria, didn’t receive maintenance therapy post-SCT, and had no death, relapse, delayed platelet or neutrophil engraftment or Grade III-IV acute GVHD for 60 days post-SCT between January 2015 and April 2020. The primary endpoint of this trial was relapse-free survival (RFS), plotted according to the Kaplan–Meier method with P-value calculated by log-rank test. Univariate and multivariate analyses were performed with cox-regression analysis. Statistical analyses were performed using R version 4.1.3. Results: The median time to AZA starting was 94（28-210）days and 62 patients (79%) received the first dose within 120 days after transplantation. The median number of AZA cycles administered was 5 (1-12). The median follow-up time was 19.6 (2.1–91.7) months for the entire cohort. AZA maintenance was related to significantly improved RFS (log-rank test, p = 0.01). The 1-year RFS was 87.7% (95% CI, 0.80-0.96) and 70.1% (95%CI, 0.62-0.79) for AZA and control cohort, respectively. OS in the AZA group was improved compared with the control group, but the difference was not statistically significant (log-rank test, p = 0.19). In a multivariable Cox regression analysis, the HR of AZA maintenance for RFS in this study was 0.19 (95% CI 0.07-0.52, p<0.001). The cGVHD remained the independent protective factor for OS (HR=0.38, 95% CI: 0.20-0.72, p=0.003) and RFS (HR=0.27, 95% CI: 0.13-0.59, p<0.001). While the status of no remission (NR) prior to HCT was an independent risk factor for OS (HR=4.39 (95% CI: 1.86-10.34, p<0.001) and RFS (HR=3.39 (95% CI: 1.63-7.08, p=0.001). According to CTCAE 5.0 grading, hematological adverse effects were the most common (79%, n=62), including neutropenia (64%, n=50), and thrombocytopenia (64%, n=50). Grade 1-2 adverse events were reported at a rate of 54% (n=42), and 28% (n=22) for Grade 3. No grade 4 adverse effects or death related to AZA occurred. Subgroup analyses were performed according to factors elaborated in methods for RFS between AZA and control groups in Figure 1. Patients with AML had superior RFS (HR=0.37, 95% CI: 0.18–0.75, p=0.01) with AZA maintenance compared to control. Additionally, AZA maintenance would be beneficial to the following subgroups: women (HR=0.28, 95% CI: 0.1–0.82, p=0.004), not “female donor – male recipient” (HR=0.48, 95% CI: 0.24–0.95, p=0.01), younger patients (age≤45, HR=0.43, 95% CI: 0.21–0.88, p=0.004), patients with younger donors (age of donors≤45, HR=0.38, 95% CI: 0.18–0.79, p=0.01), patients with favorable/intermediate-risk category(R=0.26, 95% CI: 0.10–0.70 p=0.01), and patients with matched donor (HR=0.17, 95% CI: 0.05–0.56 p=0.03).Figure 1. Forest plots showing RFS by various subgroups. Summary/Conclusion: In summary, our study concluded that AZA maintenance following allo-SCT had a positive impact on RFS for patients with high risk of recurrence. And patients with ELN favorable/intermediate-risk category could benefit from AZA maintenance therapy. Additional investigations in larger randomized controlled trials are warranted. Keywords: Azacitidine, Allogeneic hematopoietic stem cell transplant, Maintenance